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The patient who underwent the first-ever transplant of a gene-edited pig kidney into a living human was released from the hospital this week, two weeks after the groundbreaking procedure, and is recovering well so far, a transplant team at Massachusetts General Hospital (MGH) reported.
The patient experienced cellular rejection eight days after the transplant on March 16. But this is not uncommon in conventional human kidney transplants, occurring in a quarter of patients within the first three months, and the treatment was successful, said Tatsuo Kawai, MD, PhD, leader of the transplant team. Medscape Medical News.
“The patient is now off dialysis and is recovering well except for the rejection episode,” said Kawai, director of the Legorreta Clinical Transplant Tolerance Center at MGH in Boston, Massachusetts.
“This type of rejection is not uncommon in patients who receive human kidney transplants, so we know how to treat it,” he said.
After treatment with antithymocyte globulin and corticosteroids, the patient's renal function improved, Creatinine The levels have returned to normal, Kawai added.
In a press statement, the patient, identified as Richard Suleiman, 62, of Weymouth, Massachusetts, described being discharged from the hospital after a clean bill of health as “one of the happiest moments of my life.”
Suleiman had a long history Type 2 diabetes and High blood pressure In 2018, he underwent a failed kidney transplant from a human cadaveric donor at the same center, leaving him with end-stage kidney disease (ESKD).
Artificial pig model developed over 5 years of collaboration
In a four-hour operation, Suleiman received a kidney from a genetically engineered donor pig model developed over a five-year period in collaboration between MGH and eGenesis, a company based in Cambridge, Massachusetts.
Detail is Research Presentation In 2023 NatureUsing CRISPR-Cas9 gene editing technology, the scientists made 69 genomic modifications to the pig model that remove potentially harmful pig cellular sugars and inactivate viruses that can cause infections in humans.
In this model, the Yucatan miniature pig breed was specifically chosen as an ideal donor because of its organ size, which is comparable to that of humans.
Kidneys from the pig model were first transplanted into monkeys, and the transplants proved successful for up to two years.
The next experiment was to implant an artificial kidney into a brain-dead person, and since that experiment was also successful, the MGH transplant team decided that Suleyman was an ideal candidate for the groundbreaking procedure, and they applied for and received compassionate use authorization from the US Food and Drug Administration (FDA).
Immunosuppression, a key component in preventing infection
Immunosuppressive therapy used included the investigational antibody tegoprovert, a humanized immunoglobulin G1 anti-CD40 ligand antibody; RavulizumabIt is an FDA approved monoclonal antibody.
Tegoprovert, considered the basis of immune regulation in transplantation, has previously been successful in extending the functional lifespan of xenograft organs, i.e. animal organs transplanted into humans.
This medicine is Immunosuppression The second regimen in history Pig to human heart transplantThe study will take place in September 2023 at the University of Maryland Medical Center, Baltimore.
In this case, the patient died two months after transplant. In contrast, MGH surgeons said in a press statement: “our [kidney transplant] This patient is healthier than the two patients who received pig heart transplants.”
“Our study also shows that the kidneys function better than the heart,” the researchers added.
The first artificially created pig heart transplant was later found to be infected with a latent virus, but no pig-derived infection was detected in the kidney recipients, the surgical team noted.
“We remain vigilant and will continue to monitor closely for any signs of infection,” they said.
“We are pleased to be able to develop a treatment that will help improve the lives of patients with Alzheimer's disease,” said Dr Wenning Qin, research director at eGenesis. Medscape Medical News The promising results, with monkeys surviving for up to two years, give us hope that human-compatible organs will be able to demonstrate similar long-term survival. [to that of] “Our Preclinical Non-Human Primate Research”
Meanwhile, plans are underway for further transplants using pig models, Qin said.
“We are in discussions with other hospitals to perform other pig transplant procedures under FDA humane use authorization.”
Pig organ transplants without the need for immunosuppression?
Going forward, eGenesis is on a mission to develop human-compatible organs that can avoid immune suppression, Qin said.
“Our vision is to produce pig organs that do not require immunosuppression. [meaning] “Transplant patients will no longer need to take medications to suppress the immune system to prevent rejection,” she said.
“We know that additional engineering will be required, but we'll need human data to determine what that engineering will look like.”
Additional pig models are also being developed
Jamie E. Locke, MD, MPH, a transplant surgeon who helped transplant pig kidneys into brain-dead patients, said his team is working on a plan. Kidney transplantation Using different genetically engineered pig models and immunosuppressive regimens, Recent Publications.
Locke agrees that either approach holds promise for long-lasting transplants from pig donors.
“[The duration] “That's still to be determined, but we're all hopeful that the xenografts will last for the recipient's lifetime,” said Locke, professor of surgery and chief of transplantation at the University of Alabama at Birmingham Gesink College of Medicine in Birmingham, Alabama. Medscape Medical News.
“We know that pigs can live for more than 30 years outside the food chain, so we expect the organs to have a similar lifespan.”
Better than human donors?
Kawai is similarly optimistic, suggesting that genetically modified pig kidneys could indeed be superior to human donor kidneys.
“My impression is [an engineered porcine kidney] “This could be better than a cadaveric kidney transplant, because with a cadaveric kidney transplant, kidney function can be delayed and the patient may need dialysis because the kidneys don't start functioning immediately,” he said.
“In some cases, kidney function may never be restored, so this may be better than transplanting from a cadaver.”
As ESKD rates increase, long-term outcomes are predicted
According to a report by the United Network for Organ Donation (UNOS), kidneys are the most commonly needed organ for transplant, with more than 100,000 people in the United States waiting for an organ for transplant, and 17 people dying each day while waiting for an organ.
Meanwhile, in the United States, ESKD rates are projected to increase by 68% by 2030.
Given the need, news of the pig transplants is a “very encouraging event for the transplant field,” said Dr. David Klassen, UNOS chief medical officer. Medscape Medical News.
“There is still much more work to be done, including additional clinical trials and careful evaluation of long-term outcomes,” he warned.
Kawai and Classin have no disclosures to report. Locke has disclosed that his team has received grant funding from United Therapeutics. Chin is an employee of eGenesis.
